XTANDI® (enzalutamide) capsules Dosing and Administration

Convenient dosing1

XTANDI is taken as 160 mg (four 40 mg capsules) orally, once daily1

Each capsule should be swallowed whole. Instruct patients not to chew, dissolve, or open the capsules

If a dose of XTANDI is missed, inform patients that they should take it as soon as they remember

If patients forget to take their dose for the whole day, then they should take their normal dose the next day

Patients should not take more than their prescribed dose per day

XTANDI can be taken at any time during the day, but should be taken at the same time each day

Dose modifications1

If a patient experiences Grade 3-4 adverse events, the dose of XTANDI can be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose

The concomitant use of strong CYP2C8 inhibitors should be avoided if possible. If patients must be co-administered a strong CYP2C8 inhibitor, reduce the XTANDI dose to 80 mg once daily. If co-administration of the strong CYP2C8 inhibitor is discontinued, the XTANDI dose should be returned to the dose used prior to initiation of the strong CYP2C8 inhibitor

The concomitant use of strong CYP3A4 inducers should be avoided if possible. If patients must be co-administered a strong CYP3A4 inducer, increase the XTANDI dose from 160 mg to 240 mg once daily. If co-administration of the strong CYP3A4 inducer is discontinued, the XTANDI dose should be returned to the dose used prior to initiation of the strong CYP3A4 inducer

Select Safety Information

Effect of Other Drugs on XTANDI: Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of XTANDI cannot be avoided, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Straightforward administration1

Administer XTANDI orally, once daily1

Start Xtandi, Dosing

with no steroid requirement*1

without additional monitoring1

Maintain existing monitoring without a requirement for additional tests

without dose adjustments for patients with mild to severe hepatic or mild to moderate renal impairment1

XTANDI has not been evaluated in patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease

In clinical studies, XTANDI showed no increased risk of hepatic toxicity. The pharmacokinetics of XTANDI were similar in volunteers with mild, moderate, or severe hepatic impairment compared to volunteers with normal hepatic function

*In the PREVAIL trial, 27% of patients in the XTANDI arm and 30% of patients in the placebo arm received glucocorticoids for varying reasons. In the AFFIRM trial, 48% of patients in the XTANDI arm and 46% of patients in the placebo arm received glucocorticoids.1

Select Safety Information

Effect of XTANDI on Other Drugs: XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Find key information on dosing and administering XTANDI

Indication

XTANDI (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Important Safety Information

Contraindications
XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.

Warnings and PrecautionsSeizure occurred in 0.5% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors, seizures were reported in 2.2% of patients. See section 5.1 of the Prescribing Information for the list of predisposing factors. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES)In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

In the placebo-controlled study of patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the bicalutamide-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of bicalutamide patients. Discontinuations due to adverse events were reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.

Infections: In the study of patients taking XTANDI who previously received docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In the study of chemotherapy-naïve patients, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls (including fall-related injuries) occurred in 9% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug InteractionsEffect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

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